Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B.

BACKGROUND: Moderate-to-severe hemophilia B is treated with lifelong, continuous coagulation factor IX replacement to prevent bleeding. Gene therapy for hemophilia B aims to establish sustained factor IX activity, thereby protecting against bleeding without burdensome factor IX replacement. METHODS: In this open-label, phase 3 study, after a lead-in period (≥6 months) of factor IX prophylaxis, we administered one infusion of adeno-associated virus 5 (AAV5) vector expressing the Padua factor IX variant (etranacogene dezaparvovec; 2×1013 genome copies per kilogram of body weight) to 54 men with hemophilia B (factor IX activity ≤2% of the normal value) regardless of preexisting AAV5 neutralizing antibodies. The primary end point was the annualized bleeding rate, evaluated in a noninferiority analysis comparing the rate during months 7 through 18 after etranacogene dezaparvovec treatment with the rate during the lead-in period. Noninferiority of etranacogene dezaparvovec was defined as an upper limit of the two-sided 95% Wald confidence interval of the annualized bleeding rate ratio that was less than the noninferiority margin of 1.8. Superiority, additional efficacy measures, and safety were also assessed. RESULTS: The annualized bleeding rate decreased from 4.19 (95% confidence interval [CI], 3.22 to 5.45) during the lead-in period to 1.51 (95% CI, 0.81 to 2.82) during months 7 through 18 after treatment, for a rate ratio of 0.36 (95% Wald CI, 0.20 to 0.64; P<0.001), demonstrating noninferiority and superiority of etranacogene dezaparvovec as compared with factor IX prophylaxis. Factor IX activity had increased from baseline by a least-squares mean of 36.2 percentage points (95% CI, 31.4 to 41.0) at 6 months and 34.3 percentage points (95% CI, 29.5 to 39.1) at 18 months after treatment, and usage of factor IX concentrate decreased by a mean of 248,825 IU per year per participant in the post-treatment period (P<0.001 for all three comparisons). Benefits and safety were observed in participants with predose AAV5 neutralizing antibody titers of less than 700. No treatment-related serious adverse events occurred. CONCLUSIONS: Etranacogene dezaparvovec gene therapy was superior to prophylactic factor IX with respect to the annualized bleeding rate, and it had a favorable safety profile. (Funded by uniQure and CSL Behring; HOPE-B ClinicalTrials.gov number, NCT03569891.).

The endocannabinoid anandamide activates pro-resolving pathways in human primary macrophages by engaging both CB2 and GPR18 receptors.

Resolution of inflammation is the cellular and molecular process that protects from widespread and uncontrolled inflammation and restores tissue function in the aftermath of acute immune events. This process is orchestrated by specialized pro-resolving mediators (SPM), a class of bioactive lipids able to reduce immune activation and promote removal of tissue debris and apoptotic cells by macrophages. Although SPMs are the lipid class that has been best studied for its role in facilitating the resolution of self-limited inflammation, a number of other lipid signals, including endocannabinoids, also exert protective immunomodulatory effects on immune cells, including macrophages. These observations suggest that endocannabinoids may also display pro-resolving actions. Interestingly, the endocannabinoid anandamide (AEA) is not only known to bind canonical type 1 and type 2 cannabinoid receptors (CB1 and CB2) but also to engage SPM-binding receptors such as GPR18. This suggests that AEA may also contribute to the governing of resolution processes. In order to interrogate this hypothesis, we investigated the ability of AEA to induce pro-resolving responses by classically-activated primary human monocyte-derived macrophages (MoDM). We found that AEA, at nanomolar concentration, enhances efferocytosis in MoDMs in a CB2- and GPR18-dependent manner. Using lipid mediator profiling, we also observed that AEA modulates SPM profiles in these cells, including levels of resolvin (Rv)D1, RvD6, maresin (MaR)2, and RvE1 in a CB2-dependent manner. AEA treatment also modulated the gene expression of SPM enzymes involved in both the formation and further metabolism of SPM such as 5-lipoxygenase and 15-Prostaglandin dehydrogenase. Our findings show, for the first time, a direct effect of AEA on the regulation of pro-resolving pathways in human macrophages. They also provide new insights into the complex interactions between different lipid pathways in activation of pro-resolving responses contributing to the reestablishment of homeostasis in the aftermath of acute inflammation.

Dysautonomia and small fiber neuropathy in post-COVID condition and Chronic Fatigue Syndrome.

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and post-COVID condition can present similarities such as fatigue, brain fog, autonomic and neuropathic symptoms. METHODS: The study included 87 patients with post-COVID condition, 50 patients with ME/CFS, and 50 healthy controls (HC). The hemodynamic autonomic function was evaluated using the deep breathing technique, Valsalva maneuver, and Tilt test. The presence of autonomic and sensory small fiber neuropathy (SFN) was assessed with the Sudoscan and with heat and cold evoked potentials, respectively. Finally, a complete neuropsychological evaluation was performed. The objective of this study was to analyze and compare the autonomic and neuropathic symptoms in post-COVID condition with ME/CFS, and HC, as well as, analyze the relationship of these symptoms with cognition and fatigue. RESULTS: Statistically significant differences were found between groups in heart rate using the Kruskal-Wallis test (H), with ME/CFS group presenting the highest (H = 18.3; p ≤ .001). The Postural Orthostatic Tachycardia Syndrome (POTS), and pathological values in palms on the Sudoscan were found in 31% and 34% of ME/CFS, and 13.8% and 19.5% of post-COVID patients, respectively. Concerning evoked potentials, statistically significant differences were found in response latency to heat stimuli between groups (H = 23.6; p ≤ .01). Latency was highest in ME/CFS, and lowest in HC. Regarding cognition, lower parasympathetic activation was associated with worse cognitive performance. CONCLUSIONS: Both syndromes were characterized by inappropriate tachycardia at rest, with a high percentage of patients with POTS. The prolonged latencies for heat stimuli suggested damage to unmyelinated fibers. The higher proportion of patients with pathological results for upper extremities on the Sudoscan suggested a non-length-dependent SFN.

Brain fog of post-COVID-19 condition and Chronic Fatigue Syndrome, same medical disorder?

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is characterized by persistent physical and mental fatigue. The post-COVID-19 condition patients refer physical fatigue and cognitive impairment sequelae. Given the similarity between both conditions, could it be the same pathology with a different precipitating factor? OBJECTIVE: To describe the cognitive impairment, neuropsychiatric symptoms, and general symptomatology in both groups, to find out if it is the same pathology. As well as verify if the affectation of smell is related to cognitive deterioration in patients with post-COVID-19 condition. METHODS: The sample included 42 ME/CFS and 73 post-COVID-19 condition patients. Fatigue, sleep quality, anxiety and depressive symptoms, the frequency and severity of different symptoms, olfactory function and a wide range of cognitive domains were evaluated. RESULTS: Both syndromes are characterized by excessive physical fatigue, sleep problems and myalgia. Sustained attention and processing speed were impaired in 83.3% and 52.4% of ME/CFS patients while in post-COVID-19 condition were impaired in 56.2% and 41.4% of patients, respectively. Statistically significant differences were found in sustained attention and visuospatial ability, being the ME/CFS group who presented the worst performance. Physical problems and mood issues were the main variables correlating with cognitive performance in post-COVID-19 patients, while in ME/CFS it was anxiety symptoms and physical fatigue. CONCLUSIONS: The symptomatology and cognitive patterns were similar in both groups, with greater impairment in ME/CFS. This disease is characterized by greater physical and neuropsychiatric problems compared to post-COVID-19 condition. Likewise, we also propose the relevance of prolonged hyposmia as a possible marker of cognitive deterioration in patients with post-COVID-19.

Retinal Thickness Predicts the Risk of Cognitive Decline in Parkinson Disease.

OBJECTIVE: This study was undertaken to analyze longitudinal changes of retinal thickness and their predictive value as biomarkers of disease progression in idiopathic Parkinson's disease (iPD). METHODS: Patients with Lewy body diseases were enrolled and prospectively evaluated at 3 years, including patients with iPD (n = 42), dementia with Lewy bodies (n = 4), E46K-SNCA mutation carriers (n = 4), and controls (n = 17). All participants underwent Spectralis retinal optical coherence tomography and Montreal Cognitive Assessment, and Unified Parkinson's Disease Rating Scale score was obtained in patients. Macular ganglion cell-inner plexiform layer complex (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) thickness reduction rates were estimated with linear mixed models. Risk ratios were calculated to evaluate the association between baseline GCIPL and pRNFL thicknesses and the risk of subsequent cognitive and motor worsening, using clinically meaningful cutoffs. RESULTS: GCIPL thickness in the parafoveal region (1- to 3-mm ring) presented the largest reduction rate. The annualized atrophy rate was 0.63µm in iPD patients and 0.23µm in controls (p < 0.0001). iPD patients with lower parafoveal GCIPL and pRNFL thickness at baseline presented an increased risk of cognitive decline at 3 years (relative risk [RR] = 3.49, 95% confidence interval [CI] = 1.10-11.1, p = 0.03 and RR = 3.28, 95% CI = 1.03-10.45, p = 0.045, respectively). We did not identify significant associations between retinal thickness and motor deterioration. INTERPRETATION: Our results provide evidence of the potential use of optical coherence tomography-measured parafoveal GCIPL thickness to monitor neurodegeneration and to predict the risk of cognitive worsening over time in iPD. ANN NEUROL 2021;89:165-176.

Enriched Marine Oil Supplements Increase Peripheral Blood Specialized Pro-Resolving Mediators Concentrations and Reprogram Host Immune Responses: A Randomized Double-Blind Placebo-Controlled Study.

RATIONALE: Specialized pro-resolving mediators (SPM-lipoxins, resolvins, protectins, and maresins) are produced via the enzymatic conversion of essential fatty acids, including the omega-3 fatty acids docosahexaenoic acid and n-3 docosapentaenoic acid. These mediators exert potent leukocyte directed actions and control vascular inflammation. Supplementation of animals and humans with essential fatty acids, in particular omega-3 fatty acids, exerts protective actions reducing vascular and systemic inflammation. Of note, the mechanism(s) activated by these supplements in exerting their protective actions remain poorly understood. OBJECTIVE: Given that essential fatty acids are precursors in the biosynthesises of SPM, the aim of the present study was to establish the relationship between supplementation and peripheral SPM concentrations. We also investigated the relationship between changes in plasma SPM concentrations and peripheral blood platelet and leukocyte responses. METHODS AND RESULTS: Healthy volunteers were enrolled in a double-blinded, placebo-controlled, crossover study, and peripheral blood was collected at baseline, 2, 4, 6, and 24 hours post administration of placebo or one of 3 doses of an enriched marine oil supplement. Assessment of plasma SPM concentrations using lipid mediator profiling demonstrated a time- and dose-dependent increase in peripheral blood SPM concentration. Supplementation also led to a regulation of peripheral blood cell responses. Here we found a dose-dependent increase in neutrophil and monocyte phagocytosis of bacteria and a decrease in the diurnal activation of leukocytes and platelets, as measured by a reduction in adhesion molecule expression. In addition, transcriptomic analysis of peripheral blood cells demonstrated a marked change in transcript levels of immune and metabolic genes 24 hours post supplementation when compared with placebo. CONCLUSIONS: Together, these findings demonstrate that supplementation with an enriched marine oil leads to an increase in peripheral blood SPM concentrations and reprograms peripheral blood cells, indicating a role for SPM in mediating the immune-directed actions of this supplement. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03347006.

A proposed algorithm for evaluation and management of pediatric hemophilia patients who present to the emergency department with head trauma.

Hemophilia is the deficiency of plasma clotting factor VIII (hemophilia A) or IX (hemophilia B) where management focuses on the prevention and treatment of acute bleeding symptoms and their sequelae. The most concerning risk is for life-threatening bleeding, including intracranial hemorrhage (ICH), which is caused by head trauma. Guidelines exist for the evaluation and management of pediatric head trauma, including the Pediatric Emergency Care Applied Research Network (PECARN) protocol, but limited evidence exists for when hemophilia patients present to the emergency department (ED), specifically with head trauma. Literature is limited regarding ICH and hemophilia, which further supports the culture of uncertainty among providers. The objective of this study is to conduct a retrospective chart review to determine the prevalence and clinical characteristics of ICH, and to describe computed tomography (CT) scan use in hemophilia patients who present to Phoenix Children's Hospital (PCH) ED with head trauma from January 1, 2007 to June 1, 2019. A total of 89 ED visits and 43 patients met inclusion criteria, and prevalence of ICH was determined to be 4% with the patients presenting with varied clinical characteristics and few commonalities. Using these data, we propose a new algorithm to aid clinicians in determining the need for CT scan in pediatric hemophilia patients who present to the ED with head trauma.

Peripheral Blood Smear Detection of Asymptomatic Central Line Infection in a Patient With Sickle Cell Disease.

Sickle cell disease is a lifelong disorder which may be managed by chronic red cell transfusion including exchange transfusion. Chronic indwelling vascular catheters including ports offer convenient and reliable access for red cell exchange but confer risk of complications including infection and thrombosis. Detection of these complications is essential for preserving vascular access and relies on both clinical and laboratory observation. Here we describe a case of asymptomatic port infection detected by manual screening of a peripheral blood smear.

Predictors of health-related quality of life in Parkinson's disease: the impact of overlap between health-related quality of life and clinical measures.

PURPOSE: This study aimed to determine predictors of health-related quality of life (HRQoL) in Parkinson's disease (PD) and to explore their predictive value before and after controlling overlapping items between HRQoL and clinical variables. METHODS: One hundred and eight PD patients underwent motor, anxiety, depression, apathy, fatigue, and neurocognition assessment. HRQoL was assessed by the Parkinson's Disease Questionnaire-39 (PDQ-39). In order to determine predictors of HRQoL in PD, stepwise multiple regression analyses were performed in two ways: before and after removing the emotional well-being dimension from PDQ-39 to control the overlap between depression and anxiety, and HRQoL. RESULTS: HRQoL total index was predicted by anxiety, fatigue, motor symptoms, and depression, explaining 26.9%, 7.2%, 2.8%, and 1.9% of the variance. However, after removing overlapping items, HRQoL total index was predicted by fatigue (16.5%), anxiety (6.1%), motor symptoms (3.9%), and neurocognition (2.5%), but not depression. Regarding HRQoL dimensions, mobility and activities of daily living were predicted by fatigue (19.7% and 5%) and UPDRS-III (4% and 10.2%); emotional well-being by fatigue (7.9%); social support by anxiety (12.2%) and UPDRS-III (8.6%); communication by neurocognition (5.3%) and UPDRS-III (3.4%); cognition by anxiety (10.6%) and bodily discomfort by anxiety (23%) and fatigue (4.1%). CONCLUSION: These findings showed the importance of identifying and controlling overlapping items of HRQoL and clinical measures to perform an accurate interpretation. HRQoL dimensions showed different predictors before and after controlling the overlap. Based on these results fatigue, anxiety, motor symptoms, and neurocognition, but not depression are the main predictors of HRQoL in PD patients.

The maintained attention assessment in patients affected by Myalgic encephalomyelitis/chronic fatigue syndrome: a reliable biomarker?

The maintained attention is the cause of great functional limitations in CFS/ME, a disease that mainly affects women in the central period of life. Cognitive function is explored using the Montreal Cognitive Assessment, the maintained attention using the Toulouse-Piéron test with which the Global Index of Attention and Perception (GIAP) is obtained, the fatigue using the visual analog scale and the perception of effort using the modified Borg scale. The final sample were 84 patients (66 women/18 men) who met diagnostic criteria (Fukuda-1994, Carruthers-2011) and 22 healthy controls (14 women/8 men). Most of patients maintain normal cognitive function, showing low or very low attention score in the 70% of patients with a marked cognitive fatigue compared to the control group (p < 0.05). There were no significant differences between genders in GIAP or fatigue for CFS/ME; however, sick women perceive cognitive effort higher than men. Deficits in sustained attention and the perception of fatigue, so effort after performing the proposed test are a sensitive and reliable indicator that allows us to substantiate a clinical suspicion and refer patients for further studies in order to confirm or rule out CFS/ME.

Evaluating the coupling efficiency of OAM beams into ring-core optical fibers.

In optical communications, space-division multiplexing is a promising strategy to augment the fiber network capacity. It relies on modern fiber designs that support the propagation of multiple spatial modes. One of these fibers, the ring-core fiber (RCF), is able to propagate modes that carry orbital angular momentum (OAM), and has been shown to enhance not only classical but also quantum communication systems. Typically, the RCF spatial modes are used as orthogonal transmission channels for data streams that are coupled into the fiber using different free space beams. Free space beams commonly used are Laguerre-Gaussian (LG) and perfect vortex (PV) beams. Here, we study the optimal conditions to multiplex information into ring-core fibers in this scheme. We study the beam coupling efficiency using the overlap between free space beams and RCF bound beams and determine which are the most relevant LG beams to be considered and how their coupling efficiency can be maximized by properly adjusting the beam width with respect to the fiber parameters. Our results show that the coupling efficiency depends upon the OAM value and that this can limit the achievable transmission rates in SDM systems. In this regard, we find optimal coupling configurations for LG beams based on the RCF fiber and beam parameters. Further, we study the PV beam that allows for nearly perfect coupling efficiencies for all spatial modes supported by these fibers. PV beams present higher coupling efficiencies than LG beams and negligible dependence on the OAM value, thus offering an attractive solution to multiplex high counts of OAM channels from free space into a ring-core fiber using a single coupling configuration.

Language and socioemotional development in early childhood: The role of conversational turns.

This study examines the role of language environment (number of conversational turns) in the development of socioemotional competencies between 18 and 30 months. The language environment of 43 infants and their social-emotional competencies were measured at 18 months and again at 30 months. Multiple regressions showed a significant contribution of turns at 18 months on socioemotional competencies at 30 months, controlling for their initial levels, child vocalizations, maternal warmth, and social risk. Cross-lagged analysis revealed that the direction of the longitudinal relation between turns and emotional competencies is more likely to go from turns to socioemotional development than the other way around. Implications for theory and research are discussed.

Foveal Pit Morphology Characterization: A Quantitative Analysis of the Key Methodological Steps.

Disentangling the cellular anatomy that gives rise to human visual perception is one of the main challenges of ophthalmology. Of particular interest is the foveal pit, a concave depression located at the center of the retina that captures light from the gaze center. In recent years, there has been a growing interest in studying the morphology of the foveal pit by extracting geometrical features from optical coherence tomography (OCT) images. Despite this, research has devoted little attention to comparing existing approaches for two key methodological steps: the location of the foveal center and the mathematical modelling of the foveal pit. Building upon a dataset of 185 healthy subjects imaged twice, in the present paper the image alignment accuracy of four different foveal center location methods is studied in the first place. Secondly, state-of-the-art foveal pit mathematical models are compared in terms of fitting error, repeatability, and bias. The results indicate the importance of using a robust foveal center location method to align images. Moreover, we show that foveal pit models can improve the agreement between different acquisition protocols. Nevertheless, they can also introduce important biases in the parameter estimates that should be considered.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Neurological Entity?

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disorder of unknown physiopathology with multisystemic repercussions, framed in ICD-11 under the heading of neurology (8E49). There is no specific test to support its clinical diagnosis. Our objective is to review the evidence in neuroimaging and dysautonomia evaluation in order to support the neurological involvement and to find biomarkers serving to identify and/or monitor the pathology. The symptoms typically appear acutely, although they can develop progressively over years; an essential trait for diagnosis is "central" fatigue together with physical and/or mental exhaustion after a small effort. Neuroimaging reveals various morphological, connectivity, metabolic, and functional alterations of low specificity, which can serve to complement the neurological study of the patient. The COMPASS-31 questionnaire is a useful tool to triage patients under suspect of dysautonomia, at which point they may be redirected for deeper evaluation. Recently, alterations in heart rate variability, the Valsalva maneuver, and the tilt table test, together with the presence of serum autoantibodies against adrenergic, cholinergic, and serotonin receptors were shown in a subgroup of patients. This approach provides a way to identify patient phenotypes. Broader studies are needed to establish the level of sensitivity and specificity necessary for their validation. Neuroimaging contributes scarcely to the diagnosis, and this depends on the identification of specific changes. On the other hand, dysautonomia studies, carried out in specialized units, are highly promising in order to support the diagnosis and to identify potential biomarkers. ME/CFS orients towards a functional pathology that mainly involves the autonomic nervous system, although not exclusively.

PSYCOGENIC POLYDIPSIA AND SEVERE HYPONATREMIA IN BIPOLAR AFFECTIVE DISORDER.

Psychogenic polydipsia, primary polydipsia or potomania is a disorder of multifactorial etiology which is associated with substantial morbidity and mortality. It occurs frequently in patients with psychiatric diseases, particularly those with schizophrenia, however, it is not exclusive, it has been reported in a lower proportion in patients with anxiety disorders and mood disorders. Although, is still poorly understood and therefore underdiagnosed condition.

Sequenceserver: A Modern Graphical User Interface for Custom BLAST Databases.

Comparing newly obtained and previously known nucleotide and amino-acid sequences underpins modern biological research. BLAST is a well-established tool for such comparisons but is challenging to use on new data sets. We combined a user-centric design philosophy with sustainable software development approaches to create Sequenceserver, a tool for running BLAST and visually inspecting BLAST results for biological interpretation. Sequenceserver uses simple algorithms to prevent potential analysis errors and provides flexible text-based and visual outputs to support researcher productivity. Our software can be rapidly installed for use by individuals or on shared servers.

Proresolving mediator profiles in cerebrospinal fluid are linked with disease severity and outcome in adults with tuberculous meningitis.

Tuberculous meningitis (TBM) is the most lethal form of tuberculosis infection, characterized by a dysregulated immune response that frequently leads to neurologic injury and death despite the best available treatment. The mechanisms driving the inflammatory response in TBM are not well understood. To gain insights into these mechanisms, we used a lipid mediator-profiling approach to investigate the regulation of a novel group of host protective mediators, termed specialized proresolving mediators (SPMs), in the cerebrospinal fluid (CSF) of adults with TBM. Herein, using CSF from patients enrolled into a randomized placebo-controlled trial of adjunctive aspirin treatment, we found distinct lipid mediator profiles with increasing disease severity. These changes were linked with an up-regulation of inflammatory eicosanoids in patients with severe TBM and a decrease in the production of a number of SPMs. CSF proresolving mediator concentrations were also associated with 80-d survival. In survivors, we found a significant increase in proresolving mediator concentrations, including the lipoxygenase 5-derived 13-series resolvin (RvT)2, RvT4, and 15-epi-lipoxin B4, compared with those who died. Of note, treatment of patients with high-dose aspirin led to a decrease in the concentrations of the prothrombic mediator thromboxane A2, reduced brain infarcts, and decreased death in patients with TBM. Together, these findings identify a CSF SPM signature that is associated with disease severity and 80-d mortality in TBM.-Colas, R. A., Nhat, L. T. H., Thuong, N. T. T., Gómez, E. A., Ly, L., Thanh, H. H., Mai, N. T. H., Phu, N. H., Thwaites, G. E., Dalli, J. Proresolving mediator profiles in cerebrospinal fluid are linked with disease severity and outcome in adults with tuberculous meningitis.

Use of dual lumen ports for red blood cell exchange: A comparison of adults and children with sickle cell disease.

PURPOSE: Sickle cell patients receiving chronic RBC exchange require a form of long-term central venous access if peripheral access is inadequate. In adults, dual lumen (DL) ports have been utilized but associated with greater procedure complications and duration when compared to other forms of access. In the pediatric sickle cell population, the use of DL ports for RBC exchange has not been well described. In this retrospective cohort study, RBC exchange procedures utilizing DL ports in the pediatric vs adult sickle cell population were compared. METHODS: Medical records were reviewed for 685 RBC exchange procedures performed on 25 patients (11 pediatric and 14 adult) between November 2014 to November 2018. Patient-level characteristics and outcomes were compared between pediatric and adult patients using the Fisher-exact and Wilcoxon-rank sum test. Linear/logistic regression models examined procedure-level parameters and port characteristics with adjustment for clustering. RESULTS: Compared to adults, pediatric patients had slower average maximum inlet speed (42 vs 53 mL/min, P < .01), but shorter procedure time (60 vs 75 minutes, P < .01) and lower rate of access alarms (1% vs 11%, P < .01). Overall, 0.29 thrombotic events per 1000 port days and 0.04 infections per 1000 port days were observed. CONCLUSION: For adult and pediatric sickle cell patients, a DL port provides a viable option for RBC exchange. In comparison to adults, pediatric procedures with a DL port will typically be shorter and with less procedural complications due to smaller blood volumes and lower flow requirements.

Myocardial MIBG scintigraphy in genetic Parkinson's disease as a model for Lewy body disorders.

PURPOSE: To identify myocardial sympathetic denervation patterns suggestive of Lewy body (LB) pathology in patients with genetic and idiopathic parkinsonisms by 123I-metaiodobenzylguanidine (MIBG) scintigraphy. METHODS: We retrospectively analysed myocardial MIBG images acquired with a dual-head gamma camera and low-energy high-resolution collimator (LEHR) in 194 patients with suspected synucleinopathy or atypical parkinsonism, including 34 with genetic Parkinson's disease (PD; 4 PARK1, 8 PARK2 and 22 PARK8), 85 with idiopathic PD (iPD), 6 with idiopathic REM sleep behaviour disorder (iRBD), 17 with dementia with LB (DLB), 40 with multiple system atrophy (MSA) and 12 with progressive supranuclear palsy (PSP), and in 45 healthy controls. We calculated heart-to-mediastinum MIBG uptake ratios (HMR) at 15 min and 4 h (HMR4H) for the LEHR and standardized medium-energy collimators, to obtain classification accuracies and optimal cut-off values for HMR using supervised classification and ROC analyses. RESULTS: While patients with LB disorders had markedly lower HMR4HLEHR than controls (controls 1.86 ± 0.26, iPD 1.38 ± 0.29, iRBD 1.23 ± 0.09, PARK1 1.20 ± 0.09, DLB 1.17 ± 0.11; p < 0.05), for the remaining patient categories differences were smaller (PARK8 1.51 ± 0.32; p < 0.05) or not significant (MSA 1.82 ± 0.37, PSP 1.59 ± 0.23, PARK2 1.51 ± 0.30; p > 0.05). The diagnostic accuracy of HMR4HLEHR was highest in patients with LB disorders (PARK1, iPD, DLB, iRBD; 89% to 97%) and lowest in those with PARK2, PARK8, PSP and MSA (65% to 76%), with an optimal HMR4HLEHR cut-off value of 1.72 for discriminating most patients with LB disorders including iPD and 1.40 for discriminating those with aggressive LB spectrum phenotypes (DLB, PARK1 and iRBD). CONCLUSION: Our study including patients with a wide spectrum of genetic and idiopathic parkinsonisms with different degrees of LB pathology further supports myocardial MIBG scintigraphy as an accurate tool for discriminating patients with LB spectrum disorders.

Parafoveal thinning of inner retina is associated with visual dysfunction in Lewy body diseases.

BACKGROUND: Retinal optical coherence tomography findings in Lewy body diseases and their implications for visual outcomes remain controversial. We investigated whether region-specific thickness analysis of retinal layers could improve the detection of macular atrophy and unravel its association with visual disability in Parkinson's disease. METHODS: Patients with idiopathic Parkinson's disease (n = 63), dementia with Lewy bodies (n = 8), and E46K mutation carriers in the α-synuclein gene (E46K-SNCA) (n = 4) and 34 controls underwent Spectralis optical coherence tomography macular scans and a comprehensive battery of visual function and cognition tests. We computed mean retinal layer thicknesses of both eyes within 1-, 2-, 3-, and 6-mm diameter macular discs and in concentric parafoveal (1- to 2-mm, 2- to 3-mm, 1- to 3-mm) and perifoveal (3- to 6-mm) rings. Group differences in imaging parameters and their relationship with visual outcomes were analyzed. A multivariate logistic model was developed to predict visual impairment from optical coherence tomography measurements in Parkinson's disease, and cutoff values were determined with receiver operating characteristic analysis. RESULTS: When compared with controls, patients with dementia with Lewy bodies had significant thinning of the ganglion cell-inner plexiform layer complex within the central 3-mm disc mainly because of differences in 1- to 3-mm parafoveal thickness. This parameter was strongly correlated in patients, but not in controls, with low contrast visual acuity and visual cognition outcomes (P < .05, False Discovery Rate), achieving 88% of accuracy in predicting visual impairment in Parkinson's disease. CONCLUSION: Our findings support that parafoveal thinning of ganglion cell-inner plexiform complex is a sensitive and clinically relevant imaging biomarker for Lewy body diseases, specifically for Parkinson's disease. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.